Search

Background. Nasopharyngeal carcinoma (NPC) is associated with Epstein-Barr virus (EBV) and has high meta- static potential. Discoidin domain receptors (DDR1, DDR2) are receptor-type tyrosine kinases activated by collagen. Their abil- ity to induce expression of matrix metalloproteinase is related with tumor invasion. Therefore, we aim to investigate DDRs gene expression and its regulation in NPC. Methods and Results. By use of real-time quantitative poly- merase chain reaction (Q-PCR), DDR2 gene expression but not DDR1 was significantly higher in primary and metastatic NPC. DDR2 was predominantly distributed in NPC tumor cells rather than in infiltrating lymphocytes. EBV Z-transactivator (Zta) trans- fection may distinctly elevate DDR2 level. Furthermore, data from reporter assay indicate that Zta could transactivate DDR2 pro- moter activity, suggesting the possible upregulation mechanism. Conclusion. DDR2 was differentially upregulated in NPC and modulated by EBV Zta protein. DDR2 may play a role in NPC invasion and serve as a diagnostic and therapeutic target.

Background. The molecular mechanisms leading to development of nasopharyngeal carcinoma (NPC) are not well understood. To delineate the features of NPC, we tried to identify unique expression of cellular genes in the tumor bi- opsy specimens. Methods and Results. By use of a combination of differential display and cDNA microarray analysis, we found two genes, 3E5 and 4A5, to show unique expression in the NPC biopsy specimens compared with nontumor nasopharyngeal tissues. Expression of 3E5, the osteoblast-specific factor-2 (OSF-2) gene, was detected at significantly higher levels in NPC biopsy specimens than that in control tissues, a finding confirmed using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). A correlation between expression of OSF-2 and its regulatory cytokine transforming growth factor-h was ob- served in nontumor tissues but not in NPC biopsy specimens. On the other hand, expression of 4A5, whose sequences repre- sent the 3V untranslated region of the polymeric immunoglobulin receptor (pIgR) gene, was detected rarely in NPC specimens but frequently in nontumor controls. The expression of pIgR in normal epithelial cells, but not in NPC tumor cells, was verified by RT-PCR and immunohistochemical staining. Conclusions. NPC shows significant upregulation of OSF-2 and downregulation of pIgR. Expression of OSF-2 is likely to play a role in the pathogenesis of NPC. In addition, expression of OSF-2 and pIgR is disassociated with the expression of their regulatory cytokines in NPC biopsy specimens, suggesting that the tumors may have altered responses to certain cytokines. A 2005 Wiley Periodicals, Inc. Head Neck 27: 873-882, 2005

To assess the role of insulin-like growth factor 1 (IGF-1) in the growth of nasopharyngeal carcinoma (NPC), three NPC-derived cell lines, C666-1, CNE1 and HONE1, were examined. C666-1 cells maintained NPC phenotype of Epstein-Barr virus (EBV) expression and were positive for IGF-1 secretion, and their growth was strikingly inhibited by treatment with an anti-IGF-1 antibody under low serum condition. On the other hand, CNE1 and HONE1 cells were EBV-negative and did not secrete IGF-1. Although they could not grow under low serum condition, addition of recombinant IGF-1 made them grow. EBV conversion of CNE1 and HONE1 cells reproduced NPC phenotype of EBV expression and accompanied IGF-1 expression. Although they could grow under low serum condition, their growth was strikingly inhibited by treatment with the anti-IGF-1 antibody. These results suggest that EBV infection induces IGF-1 in NPC cell lines, and that the secreted IGF-1 acts as an autocrine growth factor. These findings seem to be operative in vivo, as NPC biopsies consistently express IGF-1. Further studies demonstrated that increased IGF-1 expression reflected transcriptional activation, and EBV-encoded small RNA (EBER) was responsible for IGF-1 induction. EBER is invariably expressed in EBV-associated malignancies, including NPC. The present findings strongly suggest that EBER directly affects the pathogenesis of NPC.

医薬保健研究域医学系, We compared the amount of serum Epstein-Barr virus DNA (EBV-DNA) detected in patients with nasopharyngeal carcinoma (NPC) in a high-incidence area, represented by Taiwan, and a low-incidence area, represented by Japan, using real-time quantitative PCR. The median serum EBV-DNA value in 41 Japanese NPC cases was 5450 copies/ml, and that in in 23 Taiwanese cases was 2125 copies/ml. The median serum EBV-DNA value in all 64 NPC cases was significantly higher than in control groups. Using receiver-operating-characteristic (ROC) curves, the sensitivity and specificity of EBV-DNA quantification were determined (cut-off point, 6.87 copies/ml; sensitivity, 0.855; specificity, 0.885) and compared with those of EBV-viral-capsid-antigen (VCA) titers; the results showed that EBV-DNA was a more sensitive and specific parameter than EBV-VCA titer. Then, we analyzed 19 NPC patients in whom recurrence developed (11 Japanese and 8 Taiwanese), and 26 NPC patients in continuous remission. Although there was no significant difference in EBV-DNA values between Japanese and Taiwanese patients, the value was significantly higher in the 19 patients with recurrence than in those in remission. ROC analysis again revealed a higher diagnostic value of EBV-DNA than EBV-VCA. These results suggest EBV-DNA is a more reliable tumor marker than EBV-VCA in both high-incidence and low-incidence areas of NPC.

Objective Vertigo rarely manifested as an initial symptom of nasopharyngeal carcinoma or an early symptom after irradiation; however, increasing numbers of long-term nasopharyngeal carcinoma survivors experienced it. The purpose of this study was to investigate the causes of vertigo in irradiated nasopharyngeal carcinoma survivors. Setting University hospital. Patients From January 1992 to December 2001, a total of 113 nasopharyngeal carcinoma patients (67 men and 46 women) with postirradiation vertigo consecutively visited our vertigo clinic. The mean interval from completion of irradiation to the occurrence of vertigo was 10 years. Each patient underwent otoscopic examination and a battery of audiovestibular function tests. Then, correlation between the vertigo and the radiation effect was explored. Results Postirradiation vertigo was mainly attributable to peripheral labyrinthine disorder (69%), followed by central vestibular lesions (31%). The vertiginous and associated symptoms including severity, nausea/vomiting, oscillopsia, or imbalance in cases of peripheral labyrinthine disorder were milder than those in central vestibular lesion. Meanwhile, the former had less life impact and better response to therapy compared with the latter. The mean radiation dosage in both groups was 73 +/- 6 Gy and 74 +/- 5 Gy, respectively, without a significant difference. Of these 113 patients, 85 patients (75%) had radiation otitis media in one or both ears, and 28 patients disclosed bilateral intact eardrums. The prevalence of radiation otitis media in patients with postirradiated vertigo was 53% versus 73% for those with radiation dosage less than or more than 71 Gy, respectively, exhibiting a significant difference. However, the prevalence of radiation otitis media is unrelated to radiation interval. In comparison with absent caloric responses in radiation otitis media ears, 32% versus 57% in those of less than or more than 71 Gy, respectively, indicates a significant difference. Conclusions Vertigo is a late complication in irradiated nasopharyngeal carcinoma survivors, which is mainly caused by the sequela of radiation otitis media. Because the latter is correlated with the radiation dosage, 70 Gy is recommended as the maximum dosage for nasopharyngeal carcinoma. Eradicating radiation otitis media in nasopharyngeal carcinoma survivors may subsequently prevent the postirradiation vertigo.

Objectives/Hypothesis Vascular leiomyoma, a benign tumor composed of smooth muscle cell and vascular endothelium, is rare in the head and neck region. The authors report their experience with 21 patients. Study Design Retrospective review. Methods From 1988 to 2001, the clinical records of 21 patients with vascular leiomyoma of the head and neck were reviewed. The pathological material of each tumor was reviewed again for confirmation of the diagnosis and histological classification proposed by Morimoto. Results Twelve male and 9 female patients were studied. The mean age was 48 years. The locations and numbers of cases of the tumors were as follows: auricle, five; nasal cavity, three; external nose, 3; neck, 3; lip, 3; inner canthus, 2; forehead, 1; and hard palate, 1. All tumors were painless, and most were less than 2 cm in diameter. Three vascular leiomyomas of the neck were larger than 2 cm. Two of the three tumors originating in the nasal cavity presented with nasal obstruction or epistaxis. Regarding histological subtype, 14 of 21 (67%) tumors were solid type; 6 (28%) were cavernous type, and only one (5%) was venous type. Only one tumor (5%) recurred after excision. Conclusion Vascular leiomyoma usually presents as a small, painless mass. Auricle, nose, lip, and neck are the most common sites of occurrence. Unusually large vascular leiomyomas are developed in the deep space of the neck. Imaging study or cytological examination is not helpful for diagnosis. Histological classification is not necessary. Simple excision yields excellent results.

PURPOSE: Survival in advanced nasopharyngeal carcinoma (NPC) is compromised by distant metastasis. Because mitomycin is active against hypoxic and G0 cells, which may help to eradicate micrometastasis, we investigated the effect of mitomycin-containing cisplatin-based induction chemotherapy. PATIENTS AND METHODS: Recruited for this study were American Joint Committee on Cancer (AJCC) 1992 staging system stage IV NPC patients with the following adverse features: obvious intracranial invasion, supraclavicular or bilateral neck lymph node metastasis, large neck node (> 6 cm), or elevated serum lactate dehydrogenase (LDH) level. Patients were given three cycles of chemotherapy before radiotherapy. The chemotherapy comprised a 3-week cycle of mitomycin, epirubicin, and cisplatin on day 1 and fluorouracil and leucovorin on day 8 (MEPFL). RESULTS: From January 1994 to December 1997, 111 patients were recruited. The median follow-up period was 43 months. The actuarial 5-year overall survival rate was 70% (95% confidence interval [CI], 60% to 80%; n = 111). For patients having completed radiotherapy (n = 100), the 5-year locoregional control rate was 70% (95% CI, 55% to 84%) and the distant metastasis–free rate was 81% (95% CI, 73% to 89%). The 5-year distant metastasis–free rate of N3a and N3b disease of AJCC 1997 staging system were 79% (95% CI, 62% to 95%) and 74% (95% CI, 60% to 89%), respectively. By Cox multivariate analysis, high pretreatment serum LDH level (P = .04) and neck nodal enlargement before radiotherapy (P = .001) were adverse prognostic factors of survival. CONCLUSION: The good 5-year survival of N3 disease supports the effectiveness of induction MEPFL in the primary treatment of advanced NPC. Further investigation to incorporate concurrent chemoradiotherapy is warranted.

Radiotherapy is the modality of choice for the treatment of nasopharyngeal carcinoma (NPC). However, systemic chemotherapy has recently been found to play an increasing role in the treatment of advanced or metastatic disease. The status of drug resistance gene expression that has crucial impact on chemotherapy has not been fully addressed for patients with NPC. In this study, we examined the expression of multidrug resistance 1 (MDR-1) and glutathione- S -transferase-Π (GST-Π) in primary, recurrent, and metastatic NPC using results of immunohistochemical examinations. The results were correlated with the expression of Epstein-Barr virus (EBV) latent protein, latent membrane protein 1 (LMP1), and clinicopathologic features, including stage, histopathologic types, and survival rates. MDR-1 protein expression was detected in 18 (12.6%) of 143 patients with primary NPC, 14 (32.6%) of 43 with recurrent NPC, and O (0%) of 20 with metastatic NPC, whereas 83 (58%) of 143 patients with primary NPC, 30 (69.8%) of 43 with recurrent NPC, and 13 (65%) of 20 with metastatic NPC expressed GST-Π. EBV-LMP1 was expressed in 59 (41.3%) of 143 patients with primary NPC, 23 (53.5%) of 43 with recurrent NPC, and 9 (45%) of 20 with metastatic NPC. Simultaneous expression of MDR1 and GST-Π was observed in 13 (72.2%) of 18 patients with primary NPC and 12 (85.7%) of 14 with recurrent NPC. The expression of LMP1 was detected in only 6 of the 13 patients with primary NPC and 6 of the 12 with recurrent NPC. We concluded that the expression of GST-Π was more frequent in NPC tumor tissues than the expression of MDR-1. The expression of MDR-1 correlated with clinicopathologic features of primary NPC, including the histopathologic types and survival rates, but not with disease stage. The expression of GST-Π did not correlate with clinicopathologic features. The expression of MDR-1 and GST-Π did not correlate with expression of EBV-LMP1 for patients with NPC. HUM PATHOL 32:1240-1244. Copyright © 2001 by W.B. Saunders Company

hsu m.-m., hsu w.-c., sheen t.-s. &kao c.-l. (2001) Clin. Otolaryngol.26, 334–338 Specific IgA antibodies to recombinant early and nuclear antigens of Epstein–Barr virus in nasopharyngeal carcinoma Nasopharyngeal carcinoma is a common cancer in Taiwan. The Epstein–Barr virus (EBV) is closely associated with nasopharyngeal carcinoma. The sera of patients with nasopharyngeal carcinoma have IgA antibodies to a variety of EBV latent and replicated antigens. Recently, an enzyme-linked immunosorbent assay (ELISA) kit, combining both the EBV early antigen (EA) and nuclear antigen (EBNA-1) became commercially available. The purpose of this study was to assess its clinical application. Serum IgA antibodies to the EBV EA and EBNA-1 were measured by using the ELISA kit in various groups of subjects. Fluorescence antibody (FA) tests against EBV viral capsid antigen (VCA) and EA in the IgA and IgG classes were also studied for comparison. The DNA content analysis was also carried out to investigate the association with IgA antibody titres using ELISA. The sensitivity, specificity and accuracy of the ELISA test were 98.1%, 81.8% and 88.7% respectively. It was far better than any FA tests. The IgA antibody titres showed no association with DNA content analysis. Univariate analysis of various factors revealed that IgA antibody titres were statistically correlated to N stage (P = 0.0291) and M status (P = 0.001). However, there was no association with the age, sex, T stage and clinical stage. Multivariate analysis of various factors was found to be statistically significant in patients with T4 (P = 0.0133), N3 (P = 0.0244) or M1 (P = 0.001) respectively. Serial testing of antibody titres in 22 previously untreated patients found a trend of decreasing IgA antibody titres after initial treatment when the tumours disappeared (P = 0.0358). The ELISA kit to identify specific IgA antibodies with the combination of EBV EA and EBNA-1 recombinant antigens has high sensitivity and acceptable specificity and accuracy in the diagnosis of nasopharyngeal carcinoma. This assay should be useful for early diagnosis and mass screening of patients.

The phenomenon of tumor-associated tissue eosinophilia (TATE) is seen in some cases of nasopharyngeal carcinoma (NPC) and is characterized by the eosinophils breaking through the vascular wall and pervading the tumor stroma. The margination and trans-endothelial migration of eosinophils in a typical inflammatory reaction depend on the activating effects of certain cytokines and the expression of adhesion molecules on the eosinophils and endothelial cells. In order to investigate whether the adhesion molecules and activating cytokines play a role in eosinophil tumor infiltration, we measured the serum levels of 3 adhesion molecules, intercellular adhesion molecule-1, E-selectin and vascular cell adhesion molecule-1, and 2 cytokines, IL-3 and IL-5, in 60 NPC patients and 40 normal healthy subjects. We found that the NPC patients had higher serum levels of all three soluble adhesion molecules than the normal subjects but the levels of adhesion molecules failed to correlate with the TATE phenomenon. The level...

The Zta protein is a key transactivator involved in initiating the Epstein-Barr virus (EBV) lytic cascade. In addition to transactivating many viral genes, Zta has the capacity to influence host cellular signals by binding to promoter regions or by interacting with several important cellular factors. Based on the observation that tyrosine kinases play central roles in determining the fate of cells, a kinase display assay was used to investigate whether cells expressing Zta have an altered pattern of kinase expression. The assay revealed that TRK-related tyrosine kinase (TKT) is expressed at significant levels in Zta transfectants but not in control cells. Additional evidence was obtained from Northern and Western blotting. Importantly, the upregulation of phosphorylated TKT and TKT downstream effector matrix metalloproteinase 1 in Zta transfectants hinted that TKT might initiate a signaling cascade in Zta-expressing cells. In addition, deletion analysis of the Zta protein revealed that the transactivation and dimerization domains were both essential for the upregulation of TKT transcription. Moreover, correlation of expression levels of Zta and TKT transcripts in nasopharyngeal carcinoma biopsy specimens was clearly demonstrated by quantitative PCR (Q-PCR), which provides the first evidence for an effect of Zta on cellular gene expression in vivo. These findings offer insight into the virus-cell interactions and may help us elucidate the role of EBV in tumorigenesis.

Epstein-Barr virus (EBV) infection is associated closely with the pathogenesis of nasopharyngeal carcinoma (NPC). The EBV gene product, BHRF1, has been demonstrated in vitro and is structurally and functionally similar to the oncogene bcl-2, that is able to protect cells from programmed cell death. To determine whether the BHRF1 gene is expressed in vivo, BHRF1 mRNA or protein were sought in tissues from NPC and non-NPC patients. BHRF1 transcripts were specifically detected in the NPC tumours (32 out of 44, 72.7%) rather than the non-NPC tissues (0 out of 25) by reverse transcription, polymerase chain reaction and Southern hybridization. Other EBV genes, such as the lytic gene BZLF1 and latent genes EBNA1 and LMP2A, were also investigated. BZLF1 transcripts also were found specifically in NPC tumours (33 out of 44, 75%). EBNA1 was expressed in 79.5% of NPC, and 28% of non- NPC, tissues and LMP2A was expressed in 70.5% of NPC, and 88% of non-NPC, tissues. BHRF1 protein was detected by immunohistochemistry in 4 metastatic NPC, of 36 NPC tissue sections available. The BHRF1 protein was distributed in both the nucleus and cytoplasm of the neoplastic epithelial cells. IgG antibody against the BHRF1 protein was detected in 6 of 17 (35. 3%) NPC plasma, but the protein and IgG were both absent from the non-NPC controls. BHRF1 DNA sequences were determined for 11 NPC and 3 non-NPC samples. No sequence was specific for the EBV isolates from NPC tissue. Amino acids 79 and 88 always appeared in the same form, however, for every tested isolate and both were valine or leucine. This particular characteristic was not present in the B95-8 strain or in the corresponding regions of homologues, Bcl-2 and Bcl-XL, and was regarded as unique to Oriental EBV strains.

Background Our purpose was to weigh various sonographic parameters as predicting malignant cervical lymphadenopathy and build a reliable prediction rule. Methods One hundred and eighty-nine cervical lymph node lesions from 125 consecutive patients were used for building the prediction model. Sonographic variables, including 15 morphologic features of B-mode, 5 vascular parameters of color Doppler mode, along with age and sex, were analyzed with multivariate logistic regression to evaluate the joint effect of a set of independent variables. A prediction rule for malignant lymphadenopathy was established, and prospective validation was assessed on a new group consisting of 100 lymph nodes from another 60 consecutive patients. Results The association of heterogeneous content, long transverse diameter, pathologic vascular pattern, high vascular density, and older age provided the most robust prediction value. Scoring scale was designed as 1x (age) + 2x (vascularity index) + 3x (short axis) + 4x (vascular pattern) + 4x (internal echo) according to the parameter estimates of multivariate logistic regression analysis. Cut-off value of score ≧10 as malignancy resulted in 89.2% sensitivity and 85.2% specificity. Prospective validation also showed satisfactory results (sensitivity, 82.9%; specificity, 86.2%). Conclusions By measuring only 4 sonographic parameters and age, this prediction rule could provide the physician a nonconfusing and reliable probability reference for managing cervical lymphadenopathy. © 2000 John Wiley & Sons, Inc. Head Neck 22: 223–228, 2000.

This study examined 11,333 rigid endoscopy procedures performed in the Department of Otolaryngology, National Taiwan University Hospital, during a 27-year period from 1970 to 1996. Among these cases, 3217 were performed to remove foreign bodies from the airway (459 cases, 14.3%) and esophagus (2758 cases, 85.7%). Retrospective analysis of these data revealed that peanuts (217 cases) and animal bones (1184 cases) were the most frequent foreign bodies encountered in the airway and esophagus, respectively. The successful rate of removal of these foreign bodies was 99.9% (3213/3217). The complication rate was only 0.2% (8/3217), and the mortality rate was less than 0.1% (2/3217). On the basis of these results, we conclude that foreign bodies in the airway and esophagus can be removed safely under direct visualization through rigid endoscopy with relatively few complications. A significant finding in this study is the declining trend in the number of cases in recent years. Despite the decline in the number of procedures, endoscopic removal of foreign bodies remains as a vital skill of the aerodigestive tract surgeon.

Latent membrane protein 1 (LMP-1) is the only Epstein-Barr virus (EBV)-encoded oncogenic protein that has been detected in nasopharyngeal carcinoma (NPC), a cancer that is closely associated with EBV. Previous in-vitro studies have demonstrated that LMP-1 can upregulate epidermal growth factor receptor (EGFR) in epithelial cells. It was not established whether this cellular effect exists in NPC. To assess the association between LMP-1 and EGFR in NPC tissues, 60 NPC specimens were examined by immunohistochemistry using anti-LMP-1 antibody (CS 1-4) and anti-EGFR antibodies (EGFR 1, EGFR 1005). The results revealed that 41 (68.3%) specimens were immunopositive for LMP-1 and 44 (73.3%) specimens over-expressed EGFR. Morphologically, the expressions of LMP-1 and EGFR were homogeneously distributed in the tumor nests. In addition, the correlation between LMP-1 and EGFR was statistically significant (P0.001, chi2 test, d.f. = 1). To elucidate further the correlation between LMP-1 and EGFR in vivo and in situ, an indirect dual immunofluorescence assay was conducted, using secondary antibodies conjugated with fluorescein isothiocyanate (FITC) or indocarbocyanine (Cy3). The results disclosed an intimate co-expression of LMP-1 and EGFR. In summary, the data indicate that over-expression of EGFR is a common phenomenon in NPC, and that EGFR is co-expressed with LMP-1 in NPC. Thus, EBV may play a role in the tumorigenesis of NPC through the effects of LMP-1 and EGFR.

The combination of cisplatin and 5-fluorouracil (5-FU) (PF) is the most popular regimen for treating metastatic nasopharyngeal carcinoma (NPC) but it is limited by severe stomatitis and chronic cisplatin-related toxicity. A novel approach including induction with mitomycin C, doxorubicin and cisplatin (MAP) and subsequent maintenance with weekly 5-FU and leucovorin (FL) were designed with an aim to reduce acute and chronic toxicity of PF. Thirty-two patients of NPC with measurable metastatic lesions in the liver or lung were entered into this phase II trial. Mitomycin C 8 mg m−2, doxorubicin 40 mg m−2 and cisplatin 60 mg m−2 were given on day 1 every 3 weeks as initial induction. After either four courses or remission was achieved, patients received weekly dose of 5-FU 450 mg m−2 and leucovorin 30 mg m−2 for maintenance until disease progression. With 105 courses of MAP given, 5% were accompanied by grade 3 and 0% were accompanied by grade 4 stomatitis. The dose-limiting toxicity of MAP was myelosuppression. Forty per cent of courses had grade 3 and 13% of courses had grade 4 leukopenia. No grade 3 or 4 cisplatin-related toxicity was observed. The overall response rate was 94% (95% confidence interval (CI) 84.9–100%) with a complete response rate (CR) of 6% (95% CI: 0–15.2%) and a good partial response (PR) rate of 28% (95% CI 11.7–44.6%), which was optionally defined as observance of only equivocal lesion identifiable under imaging study. Twenty-seven cases entered weekly FL maintenance phase. The median duration of maintenance with weekly FL was 38 weeks (8–91 weeks). There was no grade 3 or 4 toxicity noted during weekly FL. The median progression-free survival and overall survival were 11.6 ± 0.4 and 18.1 ± 3.6 months respectively. Six patients with a median follow-up of 19.8 months (9.6–41.0 months) were still alive and five of them had disease under control with FL. Good responders (CR and good PR) had better survival than less satisfactory responders (PR and stable disease) (P = 0.05). From Cox’s multivariate regression analysis, the only significant prognostic factor for survival was good response to MAP (P = 0.042). Liver metastasis was the only significant variable in the best subset regression model that predicted good response to MAP (CR and good PR) (P = 0.027). MAP was an effective combination for metastatic NPC with minimal stomatitis and cisplatin-related toxicity but had significant myelosuppression. Weekly FL was a maintenance therapy with minimal side-effects. The response rate and overall survival of MAP-FL were better than series previously reported even when a subset of patients with poor prognosis was selected. MAP-FL's role as neoadjuvant or adjuvant therapy is worthy of further study. © 1999 Cancer Research Campaign

Background Nasopharyngeal carcinoma (NPC) is a common head and neck cancer in Taiwan. Early detection is the best way to improve survival for this disease. A prospective study was designed to assess the feasibility of a new screening method for NPC by use of polymerase chain reaction (PCR) based on the close association of NPC and Epstein-Barr virus (EBV). Methods One hundred thirty-three different tissues from nasopharynx, nose, and sinus were investigated by use of PCR to check for the presence of EBV genome. Subsequently, from April 1996 to March 1997, 55 patients were enrolled in a prospective screening study. All patients underwent nasopharyngeal swabs before biopsy. Polymerase chain reaction detection of EBV genome was conducted on swab samples. Anti-EBV viral capsid antigen (VCA) in IgA and IgG class were checked at the same visit. Results The EBV genome was present in 91.4% (85/93) of NPC tissues and in 25.0% (10/40) of non-NPC tissues (p< .001, χ2 test). Of the 55 swabs, 49 (89.1%) specimens obtained enough cells for PCR examination. Thirty of these 49 patients were pathologically proved NPC. The presence of EBV were 86.7% (26/30) in NPC group and 42.1% (8/19) in non-NPC group. The sensitivity and specificity were 86.7% and 57.9%, respectively, which were similar to those of serologic method (87.5% and 43.5%) when the cut-off point was set at anti-VCA IgG ≥ 160 and IgA ≥ 10. Combining both methods elevates the specificity to 84.2%. Conclusions The sensitivity of this PCR screening method is similar to that of the serologic method. Combining both methods can greatly increase the specificity, indicating this new method is a good supplement to the serologic screening of this endemic disease. © 1998 John Wiley & Sons, Inc. Head Neck 20: 732–738, 1998.

The Epstein-Barr virus (EBV) open reading frame BHRF1, a homologue of the oncogene bcl-2, was cloned from a patient with nasopharyngeal carcinoma (NPC) and overexpressed in Escherichia coli. The resulting recombinant BHRF1 fusion protein, with an apparent molecular weight of 35 KD, was used as antigen in an immunoblotting assay for IgG antibody in human sera. Anti-BHRF1 antibody was detected in 57 (61.3%) of 93 patients with NPC, 5 (5.7%) of 87 patients with nonmalignant diseases of the nasopharynx, and in 1 (1.3%) of 78 healthy blood donors. The positivity rate in these nonmalignant patients was 4.4 times that of the normal controls. Negative results were observed in four patients with infectious mononucleosis and patients with other cancers, including 4 with esophageal cancer, 11 with lung cancer, 10 with lymphoma, 13 with gastric carcinoma, 10 with cervical carcinoma, and 10 with other head and neck cancers. Antibody neutralizing EBV DNase and IgA antibody to viral capsid antigen (VCA) were assayed in parallel. The results showed that 7.5% of the NPC patients were negative for anti-DNase and anti-VCA antibodies and EBV infection could be detected by the anti-BHRF1 antibody alone. The demonstration of anti-BHRF1 antibody in most NPC sera strongly supports the hypothesis that the EBV BHRF1 protein is expressed in most NPC patients and its specific antibody can be a useful marker for the diagnosis of NPC.

Our purpose was to depict the characteristics of the global vasculature of cervical lymphadenopathies and to clarify the efficiency of Doppler spectral analysis and power Doppler sonography in the differential diagnosis.Prospectively, 289 lymph node lesions underwent Doppler flow studies and were grouped as metastasis, lymphoma, tuberculosis, and benign lymphadenopathies. Sonographic assessments included vascular pattern and vascular density (presented as vascularity index) as revealed by power Doppler sonography. Vascular resistive index and pulsatility index were assessed by at least three flow samplings. Values of both the highest and the lowest resistance were analyzed. Vascularity index, resistive index, pulsatility index, nodal size, and age were correlated.Most benign lymphadenopathies (87%), tuberculous lymphadenopathies (72%), and lymphomas (71%) revealed an avascular or hilar vascular pattern. Vascular patterns of most metastatic lymphadenopathies (90%) were of spotted (26%), peripheral (11%), or mixed (53%) type. The vascularity indexes of metastatic lymphadenopathy (mean, 0.176) and lymphoma (mean, 0.122) were significantly higher than those of tuberculous and benign lymphadenopathy (mean, 0.054 and 0.042, respectively). In vascular resistance studies, the highest pulsatility index and resistive index in metastatic lymphadenopathy statistically exceeded those of benign lymphadenopathy, whereas no difference was found in the lowest values. Negative correlation was found between the vascularity index of metastatic lesions and their lowest vascular resistance, and positive correlation was found between vascularity index and nodal size in benign lymphadenopathies.In addition to vascular resistance assessed traditionally with Doppler spectral analysis, vascular pattern and vascular density assessed with power Doppler sonography can better differentiate the nature of lymphadenopathies.

Treatment of early glottic cancer is still controversial. A retrospective study was conducted to analyze the results of 49 partial vertical laryngectomies in our department. All patients except 1 were successfully decannulated. The quality of voice was suboptimal but serviceable in all patients. Overall, there were 9 recurrences: 7 in the larynx and 2 in the neck. In the laryngeal recurrence group, 5 of 6 patients were successfully salvaged with total laryngectomy. One patient died of acute renal failure 1 month after salvage operation. Another patient survived 4.5 years after cisplatin-based chemotherapy. In the neck recurrence group, 1 patient was successfully salvaged with neck dissection; the other was lost to follow-up after neck dissection. The actuarial 5-year survival rate was 97.4% and the larynx preservation rate was 88%. The recurrence rate was 14%, when 2 of the 7 laryngeal recurrences were excluded because they occurred beyond 5 years. The results of this series were encouraging. We suggest that partial vertical laryngectomy is a good treatment modality for selected early glottic cancers, especially those of the T1 group.

From the Departments of Otolaryngology (Drs. Sheen and Ko), Pathology (Drs. Chang and Wu), and Oncology (Dr. Yeh), National Taiwan University Hospital. Reprint requests: Yih-Leong Chang, MD, Department of Pathology, National Taiwan University Hospital, No. 7, Chung-Shan South Rd., Taipei, Taiwan. Otolaryngol Head Neck Surg 1998;118:408-11. Copyright © 1998 by the American Academy of Otolaryngology– Head and Neck Surgery Foundation, Inc. 0194-5998/98/$5.00 + 0 23/78/77260 Sinus histiocytosis with massive lymphadenopathy was first reported by Rosai and Dorfman1, 2 in 1969. Until 1990, 423 patients were enrolled in the registry.3 These patients usually had bilateral, painless, and extensive cervical lymphadenopathy. The involved lymph nodes showed pericapsular fibrosis with abundant histiocytes. These histiocytes were large and contained vesicular nuclei, delicate nuclear membrane, distinct nucleoli, voluminous pale cytoplasm, and often with phagocytosed lymphocytes. This phenomenon was referred to as emperipolesis.4, 5 This disease was usually benign and was differentiated from some malignant diseases such as malignant lymphoma or Hodgkin’s disease. Approximately 40% of the patients also had extranodal involvement.3 Moreover, extranodal involvement was sometimes the initial and sole manifestation of the disorder. The condition was similar to nodal disease with typical histiocytes but without the nodal capsule or subcapsular sinusoid. A sole extranodal involvement in the head and neck region was occasionally reported in the literature.6-15 A 15-year-old boy was referred to us because of nasal obstruction and nasal bleeding. A nasal mass was found in his right nasal cavity. RosaiDorfman disease was proved after pathologic examination of this nasal mass was performed.

BACKGROUND. Undifferentiated carcinoma of the salivary glands is a rare disease, the incidence of which is highest among the Inuit of Greenland and North America. It was demonstrated to be closely related to Epstein- Barr virus (EBV) infection. However, the relation of EBV to this tumor has not been studied to any great extent here in Taiwan because of the small number of cases. METHODS. Twelve cases of undifferentiated carcinoma of the salivary glands from the period 1977-1996 were retrieved from the cancer registry at National Taiwan University Hospital. The clinical data were analyzed retrospectively based on the medical records. Eleven formalin fixed, paraffin embedded tissue sections were used for in situ hybridization with an antisense probe complementary to EBV-encoded RNA 1 (EBER1). RESULTS. Ten of 12 tumors originated from the parotid gland and 2 from the submandibular gland. The patients' ages ranged from 22 to 63 years, with an average of 38.1 years. One patient was lost to follow-up, 2 patients died of metastatic disease, and the remaining 9 patients were all alive and disease free at last follow-up. The actuarial 5-year survival rate was 79.8%. In situ hybridization demonstrated EBER1 in 9 of the undifferentiated carcinomas with lymphoid stroma, but EBER1 was not demonstrated in the other 2 tumors without lymphoid stroma. CONCLUSIONS. Undifferentiated carcinoma with lymphoid stroma of the major salivary glands is closely associated with EBV. The mainstay of treatment is surgery and postoperative radiotherapy. The outcomes in this series were good except for two elderly patients who died of rapid and progressive distant metastases.

Objective: To evaluate the effectiveness of salvage neck dissection as part of a multidisciplinary treatment approach in persistent or recurrent metastatic nasopharyngeal carcinoma, after failure of initial radiotherapy at the regional site. Design: A retrospective study of 31 patients treated during a 14-year period from March 1981 through May 1995, with a maximum follow-up of 152 months. Factors evaluated include patients' sex, age, and initial stage of tumor, mobility and number of nodal recurrences, surgical and pathological findings, and postoperative irradiation. Setting: Academic tertiary referral center. Patients: Twenty-six men and 5 women were studied; one patient had neck dissection to both sides of the neck on separate occasions, for a total of 32 operations. All patients had pathologically proved nasopharyngeal carcinoma and had been previously treated at the primary site and both sides of the neck with definitive radiotherapy. Intervention: Patients underwent a radical, modified radical, or level I—sparing radical neck dissection. Main Outcome Measure: Surgical morbidity, time to recurrence at the regional site, and survival time. Results: Clinically, there was a disease predilection of 81% at levels II and V. Surgical morbidity was minimal. Regional control was achieved in 20 (65%) of the patients, and the overall 5-year survival was 67%. Tumor involvement of the posterior triangle musculature and spinal accessory nerve was associated with failure to control neck disease. Extracapsular nodal extension correlated with a poor survival outcome. Conclusion: Control of regional disease by salvage neck dissection when radiotherapy has failed is both safe and effective in properly selected patients. Arch Otolaryngol Head Neck Surg. 1997;123:725-729

Nasal packing is a very common procedure in the otolaryngologic service for nasal bleeding and postoperative hemostasis. However, a pyogenic granuloma complicated from nasal packing has not been reported in the literature. A 50-year-old man underwent nasal packing by use of vaseline gauze due to nasal bleeding. Two weeks later, a dark brown nasal tumor was found in his nasal cavity. He underwent partial turbinectomy for removal of the tumor. The pathology demonstrated a pyogenic granuloma. It is the first case of a confirmed pyogenic granuloma complicated from nasal packing in the literature. To prevent complications and decrease the discomfort, we strongly recommend the use of inflatable balloons or nontraumatic materials for nasal packing.

Objective: To assess the efficacy of salvage surgery for patients with recurrent nasopharyngeal carcinoma (NPC) at the primary site after radiotherapy. Design: Retrospective analysis of 24 patients treated by transpalatal, transmaxillary, or transmandibular approach to resect the recurrent tumor, with maximum follow-up of 50 months. Setting: Academic tertiary referral center. Results: Radiotherapy before salvage surgery included 1 to 3 courses of radiation to the nasopharynx, with doses ranging from 60 to 190 Gy. Eighteen (75%) of the patients relapsed within 2 years, and 6 (25%) relapsed more than 6 years after the last irradiation. In 4 of 6 laterelapsing cases, the histopathological type changed to keratinizing squamous cell carcinoma, which is rare in cases of NPC in Taiwan. Fourteen patients (58%) survived for 8 to 50 months after surgery (median, 18 months). The surgical complications were tolerable. Conclusions: Salvage surgery is feasible in selected patients with recurrent disease at the primary site. Thus, we can offer alternative retreatment in addition to external irradiation for patients with recurrent NPC. Arch Otolaryngol Head Neck Surg. 1997;123:305-309

Background Laryngeal sarcoma is a rare disease entity. In review of the literature, chondrosarcoma is the most common sarcoma, followed by fibrosarcoma. Osteosarcoma is very rare; there are only seven cases reported in the literature. Postirradiation sarcoma is a late complication of radiotherapy. Osteosarcoma is the most common type in this group. The larynx is often involved in the radiation field of treatment for head and neck malignancies. However, postirradiation laryngeal osteosarcoma has not yet been reported. Methods We present a 56-year-old man who underwent radiotherapy for nasopharyngeal carcinoma 32 years ago and later developed a laryngeal osteosarcoma. Results The patient underwent total laryngectomy but died 1 year and 9 months later with locally extensive disease. Conclusions We report the first case of postirradiation laryngeal osteosarcoma. In addition to surgical treatment, adjunctive therapies should be considered for this group of patients. © 1997 John Wiley & Sons, Inc. Head Neck 19, 57–62, 1997.

Background The internal carotid artery, the internal jugular vein, and the spinal accessory nerve are the main structures that are preserved in conservative neck dissections. In the upper neck, one surgical landmark used to find these structures is the transverse process of a cervical vertebral body. There is controversy about the origin of the transverse process in the upper neck. Methods We applied three-dimensional computerized tomography (3-D CT), an intraoperative navigational system and cadaver dissection of the neck to clarify the controversy. Results The origin of the transverse process was from the atlas (C1). Conclusions The transverse process of the atlas is an important surgical landmark in the upper neck. The neurovascular bundle is located anteriorly. The transverse process of the axis (C2) is less prominent and is situated antero-inferior to the spinal accessory nerve where the nerve emerges from the posterior border of the internal jugular vein. © 1997 John Wiley & Sons, Inc. Head Neck 19: 37–40, 1997.

Extraskeletal Ewing’s sarcoma/primitive neuroectodermal tumour (EES/PNET) is a rare disease entity. Scalp EES/PNET has been reported rarely. We report a case of an 11-year-old boy who had painful and rapidly growing subcutaneous nodes over the scalp and neck. The final diagnosis was EES/PNET after biopsy and immunohistochemical assay. The patient underwent surgical excision, chemotherapy and radiotherapy with a dose of 2000 cGy. Now he has been free of disease for two years. Early awareness and treatment of this rare disease, and wide resection followed by chemotherapy and radiotherapy might improve patients’ long-term survival.

Background. Inhibitors of apoptosis proteins (IAPs), which counteract apoptosis by potently inhibiting caspase activation, are promising targets of new anti-tumor therapy. However, their roles in the pathogenesis of nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-associated carcinoma, are not fully understood. Herein, we investigated the expression and regulation of IAPs in NPC. Methods and Results. Using real-time quantitative polymerase chain reaction (PCR) analysis, we found that among the IAPs family only the transcription of survivin, HIAP-1, and HIAP-2 was consistently up-regulated in NPC and metastatic NPC tissues. Immunohistochemical staining showed that their proteins were more predominantly expressed in tumor cells nests. Noteworthy, these IAPs were upregulated by interleukin-1α stimulation or EBV infection, and subsequently resulted in triggering rapid proliferation of NPC verified by strong Ki-67 staining. Conclusion. Survivin, HIAP-1, and HIAP-2 were distinctly upregulated in NPC, suggesting they may play significant roles in NPC tumorigenesis and serve as tumor markers with prognostic and therapeutic implications. © 2008 Wiley Periodicals, Inc. Head Neck, 2008

Nonkeratinizing nasopharyngeal carcinoma (NPC) is 100% associated with Epstein-Barr Virus (EBV) and divided into two subtypes (WHO types II and III) based on histology. We tested whether these subtypes can be distinguished at the molecular genetic level using an algorithm that analyzes sets of related genes (gene set enrichment analysis). We found that a class of IFN-stimulated genes (ISG), frequently associated with the antiviral response, was significantly activated in type III versus type II NPC. Consistent with this, replication of the endogenous EBV was suppressed in type III. A strong association was also seen with a subset of ISGs previously identified in systemic lupus erythematosus, another disease in which ‘normal’ EBV biology is deregulated, suggesting that this pattern of ISG expression may be linked to the increased EBV activity in both diseases. In contrast, unsupervised hierarchical clustering of the complete expression profiles failed to distinguish the two subsets. These results suggest that type II and III NPC have not originated from obviously distinct epithelial precursors; rather, the histologic differences may be a consequence of a differential antiviral response, involving IFNs, to chronic EBV infection. [Cancer Res 2007;67(2):474–81]

Nonkeratinizing nasopharyngeal carcinomas (NPC) are >95% associated with the expression of the Epstein-Barr virus (EBV) LMP2A latent protein. However, the role of EBV, in particular, LMP2A, in tumor progression is not well understood. Using Affymetrix chips and a pattern-matching computational technique (neighborhood analysis), we show that the level of LMP2A expression in NPC biopsy samples correlates with that of a cellular protein, integrin-alpha-6 (ITGα6), that is associated with cellular migration in vitro and metastasis in vivo. We have recently developed a primary epithelial model from tonsil tissue to study EBV infection in epithelial cells. Here we report that LMP2A expression in primary tonsil epithelial cells causes them to become migratory and invasive, that ITGα6 RNA levels are up-regulated in epithelial cells expressing LMP2, and that ITGα6 protein levels are increased in the migrating cells. Blocking antibodies against ITGα6 abrogated LMP2-induced invasion through Matrigel by primary epithelial cells. Our results provide a link between LMP2A expression, ITGα6 expression, epithelial cell migration, and NPC metastasis and suggest that EBV infection may contribute to the high incidence of metastasis in NPC progression.

The BARF1 gene is located in the BamHI-A fragment of the Epstein-Barr virus (EBV) genome, encodes 221 amino acids, and has activity as an oncogene. Several reports have demonstrated that BARF1 is expressed in the tissues of various EBV-associated epithelioid malignancies. However,BARF1 is thought to be a lytic gene, since its expression is induced upon induction of the lytic cycle in Burkitt's lymphoma cell lines. Therefore, the possibility cannot be excluded that BARF1 expression in EBV-associated epithelioid malignancies reflects spontaneous induction of the lytic cycle in carcinoma cells. The present study aimed to clarify whether BARF1 was expressed as a latent gene or a lytic gene in epithelioid malignancies. Quantitative real-time RT-PCR assay revealed that BARF1 was highly expressed in nasopharyngeal carcinoma (NPC) and EBV-positive gastric carcinoma tissues in the absence of expression of lytic genes. On the other hand, BARF1 protein was detectable only in two of seven NPC tissue samples by immunoblot analysis. Analysis of BARF1-transfected CNE1 cells revealed that BARF1 was quickly secreted into culture medium and was hardly detectable in the cell lysate, which would account for why some NPC tissues were negative for BARF1 protein expression even though they were strongly positive forBARF1 expression at the transcriptional level. The present findings indicate that BARF1 is expressed in NPC and EBV-positive gastric carcinoma tissues as a latent gene and suggest that BARF1 plays a role in the pathogenesis of these malignancies. Copyright 2005 Wiley-Liss, Inc.

The Epstein-Barr Virus (EBV) latent membrane protein 1 (LMP1) has a significant role in several malignancies, including nasopharyngeal carcinoma (NPC). LMP1 is the principal oncoprotein, and we have shown that it also induces a set of factors that mediates invasion, angiogenesis and metastasis. Matrix metalloproteinase-1 (MMP1) is also involved in several malignancies. A single guanine insertion polymorphism (2G) in the MMP1 promoter creates an Ets binding site that causes high levels of transcription and correlates with risk for some malignancies. Here, we evaluate the impact of this 2G insertion type on NPC. We genotyped 44 Japanese and 39 Taiwanese NPC patients, as well as 58 Japanese and 23 Taiwanese healthy controls. The proportion of 2G homozygotes was higher in the NPC groups than in controls (Japanese: p = 0.02, odds ratio (OR) = 2.49; Taiwanese: p = 0.02, OR = 3.66). An analysis of overall survival rates in the patients with NPC, and the 1G/1G genotype disclosed a favorable prognosis (5-year survival rate = 100%, p = 0.04). Multivariate analysis showed that 1G/1G has independent prognostic significance. We also examined whether LMP1 enhances MMP1 expression in epithelial cells in culture. LMP1-transfected cells with 2G/2G genotype expressed MMP1, which was abolished by activator protein-1 (AP1) dominant-negative (DN) and Ets-DN. LMP1 also induced active MMP3, which can cleave latent MMP1, and AP1-DN and Ets-DN suppressed the MMP3 expression. These results suggest that LMP1-induced MMP1 and MMP3 are closely linked and show that LMP1 activates MMP1 via an Ets binding site formed by 2G, which is a candidate marker for both risk and prognosis of NPC.

BACKGROUND Undifferentiated carcinomas of the major salivary glands are rare malignant neoplasms of the head and neck region, and patients with these lesions have a poor prognosis. Patients with lymphoepithelial carcinoma (LEC), a specific subtype of undifferentiated carcinoma, however, have a better prognosis, and LEC seems to differ from large cell undifferentiated carcinoma (LCUC) clinically. METHODS Sixteen patients with LEC and 12 patients with LCUC were retrieved from the records of 295 patients who had malignancies of the major salivary glands. A retrospective study on clinical manifestations, treatments, long-term outcomes, and an association with Epstein–Barr virus (EBV) by EBV-encoded small RNA-1 in situ hybridization was conducted to identify their differences. RESULTS The median patient age was 44.5 years in the LEC group and 56 years in the LCUC group. At the time of presentation, patients with LCUC had a history of rapid-growing tumor and more advanced locoregional disease (Stage IV in 75% of patients with LCUC compared with 13% of patients with LEC). All 16 patients with LEC underwent curative surgery and radiotherapy, and their 5-year survival rate was 85.6%. In the LCUC group, only 7 patients were eligible to undergo radical surgery and receive radiotherapy, and their 2-year survival rate was only 36%. Age > 50 years was associated with a significantly worse prognosis for patients with LCUC. Neck metastasis and tumor size > 6 cm tended to be poor prognostic factors. Tumors were positive for harboring the EBV genome in all 16 LEC samples but in none of the LCUC samples. CONCLUSIONS The clinicopathologic features of LEC and LCUC of the major salivary glands were different. LEC was associated with EBV, and patients with LEC had a much better prognosis compared with the prognosis for patients with LCUC. Therefore, LEC should be put in an independent group and should not be included in the same category as undifferentiated carcinomas of the salivary gland. Cancer 2004. © 2004 American Cancer Society.

Immune responses to three Epstein-Barr virus (EBV) lytic proteins, DNase, thymidine kinase (TK), and BMRF-1 gene products (50/52 kDa diffused early antigen, EA-D complex) were determined in EBV-infected control individuals and patients with nasopharyngeal carcinoma (NPC). Immunofluorescence assays (IFA) were used to detect their humoral immune responses using recombinant EBV lytic proteins expressed in a baculovirus system as antigens. Cell proliferation assays were performed to evaluate their cellular immune responses by monitoring 3H-thymidine incorporation. Seventy patients with NPC and 32 non-cancer controls were analyzed. The results of IFA showed antibody titers to all three EBV lytic proteins to be higher in the patients with NPC especially for the IgA class. Positivity rates of the three IgA antibodies also were higher in the patients with NPC population. Furthermore, the profiles of the IgA antibodies correlated with those to total early antigens (EA) expressed in the early phase and viral capsid antigen (VCA) expressed in the late phase, of EBV replication. The most interesting finding was that antibody titers to the three EBV lytic proteins were associated significantly with metastases of cervical lymph nodes in patients with NPC. As for cellular immunity to the EA-D complex and DNase, weak responses were observed in the cell proliferation assays. Peripheral blood cells from most individuals could not be stimulated to proliferate, except for a few patients with NPC whose antibody titers against the EA-D complex and DNase also were very high.

Nasopharyngeal carcinoma (NPC) is distinctive in head and neck carcinomas for its close association with Epstein-Barr virus and its highly metastatic nature. Up-regulation of cell motility is essential for enhancement of metastatic potential. The expression of c-Met proto-oncogene, a high-affinity receptor for hepatocyte growth factor/scatter factor, has been reported to correlate with metastatic ability of the tumor cell. We observed close association of c-Met expression with cervical lymph node metastasis (P = 0.0272) in 39 NPC specimens studied immunohistochemically. Epstein-Barr virus-encoding latent membrane protein-1 (LMP-1) is a primary oncogene and is suggested to enhance the metastatic property of NPC. Previously, we reported that LMP-1 enhanced the motility of Madin-Darby canine kidney (MDCK) epithelial cells that was mediated by activation of Ets-1 transcription factor. Therefore, we examined the interrelationships of LMP-1, Ets-1, and c-Met. In immunohistochemical studies, the expression of LMP-1, Ets-1, and c-Met correlated significantly with each other in NPC (LMP-1 versus Ets-1, P < 0.0001; Ets-1 versus c-Met, P = 0.0012; LMP-1 versus Met, P = 0.0005). Transfection of LMP-1-expressing plasmid in MDCK cells induced c-Met protein expression. The c-Met protein was also induced by Ets-1 expression, and induction of c-Met by LMP-1 was suppressed by introducing a dominant-negative form of Ets-1 in LMP-1-expressing MDCK cells. These results suggest that LMP-1 induces c-Met through the activation of Ets-1, which may contribute in part to the highly metastatic potential of NPC.

BACKGROUND Nasopharyngeal carcinoma (NPC) is a highly metastatic carcinoma whose consistent association with Epstein–Barr virus (EBV) has been established. Latent membrane protein 1 (LMP1), an EBV membrane protein expressed in latent infection, is considered to be the EBV oncoprotein. Matrix metalloproteinase 9 (MMP9), one of the MMP families, degrades Type IV collagen, a major component of extracellular matrix and is believed to be crucial for cancer invasion and metastasis. Although MMP9 is reported to be expressed in a variety of cancers, no reports concerning NPC have been published to date to the authors' knowledge. Recently, the authors have shown that LMP1 induces MMP9 in vitro cell line, which suggests the possibility of a mechanism in which LMP1 of EBV contributes to the metastasis and tumorigenesis of NPC by the induction of MMP9. METHODS The expressions of LMP1 and MMP9 were immunohistochemically examined in 38 NPC sections, and the relation of these proteins were statistically analyzed. The authors also analyzed the associations of these proteins with clinical features. RESULTS Both LMP1 and MMP9 proteins were predominantly immunolocalized in cancer nests. The expression of MMP9 showed a significant positive correlation with the expression of LMP1 (r = 0.75; P < 0.0001). Also, the expression of MMP9 correlated with lymph node metastasis (P = 0.0004). CONCLUSIONS The results suggest that the induction of MMP9 by LMP1 contributes to the metastatic potential of NPC. Cancer 2000;89:715–23. © 2000 American Cancer Society.

Herpes zoster oticus is a cranial polyneuropathy with facial nerve involvement as its main feature. The prognosis of the facial palsy is usually poor. Thirty patients with herpes zoster oticus suffering from facial palsy were admitted for parenteral acyclovir and oral prednisolone. Multiple regression analysis of improvement of facial palsy showed three significant covariates: age, multiple nerve palsies, and the initial grading of the palsy. The recovery of the facial palsy treated with acyclovir and prednisolone was good, and possibility of a good outcome was greater when the initial grade of the palsy was higher. Multiple nerve palsies and age had negative effects on the improvement.

In this investigation we dissected 3 cadavers with the lateral cervical approach to assess the usefulness of the transverse process of the atlas (TPA) as a reference guide in the upper lateral neck. Our results indicate that all the important structures in this space can be identified systematically. Lateral to the TPA sits the posterior belly of the digastric muscle, the stylohyoid muscle, and the occipital artery. Anterior to the TPA, the styloid process can be exposed. The internal jugular vein and cranial nerves X, XI, and XII sit between the styloid process and the TPA. Superior to the TPA, tracing the carotid sheath upward, the carotid canal and jugular foramen can be reached. Anteroinferior to the jugular foramen, the hypoglossal nerve emerges from the cranial cavity through the hypoglossal canal. Posterior to the TPA, the suboccipital triangle can be recognized. Within the triangle, the vertebral artery and its accompanying venous complex can be identified. (Otolaryngol Head Neck Surg 2000;122:284-9.)

Metastatic cancer to the palatine tonsil is extremely rare. We describe a 66-year-old man who was diagnosed with hepatocellular carcinoma 2 years previously and who had the sensation of having a lump in his throat for 1 month before presentation. One reddish-blue, ulcerated, granular tumor was found at his right tonsillar fossa. After tonsillectomy, pathology showed metastatic hepatocellular carcinoma. The patient died from sepsis and hepatic failure 9 months later.

Background Mutagen sensitivity tested with bleomycin sulfate can determine a susceptible phenotype, which is relevant only in organs and tissues that have direct contact with the external environment. Patients with head and neck cancers have more mutagen sensitivity than control subjects without cancer, and the hypersensitive phenotype has a risk for the development of a second primary cancer. Head and neck cancers, however, represent a heterogeneous group of neoplasm. The biological behavior of nasopharyngeal carcinoma (NPC) and other head and neck cancers differs. Objective To evaluate the difference in mutagen sensitivity among patients without cancer, patients with NPC, patients with oral or oropharyngeal cancer (ORC), and patients with laryngeal or hypopharyngeal cancer (LHC). Design Peripheral blood was cultured at 37°C, using 5% carbon dioxide, for 72 hours. After 67 hours of incubation, bleomycin in a concentration of 30 IU/L was added to induce chromatid breaks. The number of chromatid breaks per cell was scored in 50 metaphases of cultured lymphocytes and compared in the 4 groups. Subjects Patients with histologically proven squamous cell carcinoma of the mucosa of the upper digestive tract, which included 3 groups: patients with NPC, patients with ORC, and those with LHC. Control subjects were hospital inpatients with no tumor history. There were 35 patients in each group. Results The mean (±SD) number of breaks per cell in the control group and in the groups with NPC, ORC, and LHC were 0.80 (±0.32), 1.03 (±0.45), 1.30 (±0.44), and 1.35 (±0.46), respectively. All the cancer groups had significantly higher mean breaks per cell and a higher prevalence of hypersensitivity than the control group. Patients with NPC had a significantly lower mean number of breaks per cell than the group with ORC or that with LHC. Conclusions Patients with NPC had less mutagen sensitivity than those with ORC or LHC. Our results support the clinical and epidemiological findings of a difference between NPC and other head and neck cancers. Environmental factors might play a less pronounced role in the carcinogenesis of NPC.

Nineteen nasopharyngeal carcinoma (NPC) patients were subjected to eustachian tube function testing before and 5 years after irradiation. Tubal patency and clearance function of the eustachian tube showed deterioration if maximum irradiation dosage was more than 70 Gy, whereas dynamic function of the eustachian tube was preserved. Development of middle ear complications in NPC patients post-irradiation was caused by both tubal and inflammatory factors. To preserve tubal function, maximum irradiation dosage to NPC should be limited to 70 Gy. To decrease the inflammatory reaction, firstly, middle ear effusion should be drained by repeated myringotomies instead of grommet insertion, and secondly, sinusitis should be evaluated and treated, because sinusitis can aggravate otitis media with effusion.

We present a patient with an esophageal foreign body complicated by severe esophageal stricture, which progressed to complete stricture after a period of follow-up. Transthoracic resection of the stricture with end-to-end anastomosis seemed to be a successful treatment in this transmural stricture. The treatment of esophageal stricture is well discussed.

Objectives: To evaluate the incidence rate of nasopharyngeal carcinoma with dermatomyositis, the influence of dermatomyositis on clinical course, and complications and survival of patients with nasopharyngeal carcinoma after radiotherapy. Design: A retrospective study of 12 patients with nasopharyngeal carcinoma associated with dermatomyositis, with a maximum follow-up of 228 months. Setting: Academic tertiary referral center. Patients: There were 6441 new patients with nasopharyngeal carcinoma who were seen at the National Taiwan University Hospital, Taipei, during the period from 1970 through 1993. Twelve patients were found to have dermatomyositis. Main Outcome Measure: Clinical manifestations of nasopharyngeal carcinoma with dermatomyositis. Results: Twenty-seven (26%) of 104 patients with dermatomyositis had an associated malignancy. Twelve of these patients were diagnosed as having nasopharyngeal carcinoma. The typical skin manifestation of dermatomyositis was found in all 12 patients. Myopathy occurred in 10 patients. Three patients died of recurrence of nasopharyngeal carcinoma, one died of a second malignancy, one died of upper gastrointestinal bleeding, and one became unavailable for follow-up. The other six patients have had disease-free survival, with a mean follow-up period of 100.5 months (range, 5 to 228 months). The 1-year survival rate was 83.8%, and the 5-year survival rate was 69.4%. Conclusions: In Taiwan, dermatomyositis is associated with an increased incidence rate of nasopharyngeal carcinoma. A search for nasopharyngeal carcinoma in patients with dermatomyositis should be performed in areas prevalent for nasopharyngeal carcinoma. If present, nasopharyngeal carcinoma can precede, occur concurrently with, or follow the diagnosis of dermatomyositis. Treatment of nasopharyngeal carcinoma may affect myositic or cutaneous disease. The prognosis and survival rates of nasopharyngeal carcinoma remained unaffected by dermatomyositis. No complications were noted owing to the radiotherapy used to treat dermatomyositis. (Arch Otolaryngol Head Neck Surg. 1995;121:1298-1301)